rebastinib (DCC-2036) / Ono Pharma 
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 8 Diseases   1 Trial   1 Trial   98 News 


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  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    TMEM DOORWAYS ARE AN ACTIONABLE TARGET IN PANCREATIC ADENOCARCINOMA (Adams) -  Jun 20, 2023 - Abstract #APCM2023APCM_24;    
    TMEM doorway concentration is significantly associated with PDAC tumor grade and decreases with neoadjuvant therapy. Inhibition of Tie2 with the selective inhibitor, rebastinib, preclinically leads to decreased TMEM doorway function and dissemination in PDAC.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    TMEM DOORWAYS ARE AN ACTIONABLE TARGET IN PANCREATIC ADENOCARCINOMA (Room S505) -  May 11, 2023 - Abstract #SSAT2023SSAT_283;    
    TMEM doorway concentration is significantly associated with PDAC tumor grade and decreases with neoadjuvant therapy. Inhibition of Tie2 with the selective inhibitor, rebastinib, preclinically leads to decreased TMEM doorway function and dissemination in PDAC.
  • ||||||||||  MLi-2 / Merck (MSD), rebastinib (DCC-2036) / Deciphera
    Journal:  Capturing Differences in the Regulation of LRRK2 Dynamics and Conformational States by Small Molecule Kinase Inhibitors. (Pubmed Central) -  Apr 24, 2023   
    By probing the distinct effects of the type I and type II inhibitors, key interdomain interactions are found to regulate the communication between the kinase domain and the GTPase domain. The intermediate states revealed in our simulations facilitate the efforts toward in silico design of allosteric modulators that control LRRK2 conformations and potentially mediate the oligomeric states of LRRK2 and its interactions with other proteins.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    Journal:  The Bcr-Abl inhibitor DCC-2036 inhibits necroptosis and ameliorates osteoarthritis by targeting RIPK1 and RIPK3 kinases. (Pubmed Central) -  Apr 3, 2023   
    A mechanistic study showed that DCC-2036 directly inhibited the activities of RIPK1 and RIPK3 kinases to block necroptosis, inhibiting the inflammatory response and protecting chondrocytes. In summary, our research suggests that DCC-2036, a new necroptosis inhibitor targeting RIPK1 and RIPK3 kinase activity, may be useful for the clinical treatment of OA and provides a new direction for the research and treatment of OA.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    TMEM DOORWAYS ARE AN ACTIONABLE TARGET IN PANCREATIC ADENOCARCINOMA (S505 - McCormick Place) -  Mar 23, 2023 - Abstract #DDW2023DDW_5457;    
    TMEM doorway concentration is significantly associated with PDAC tumor grade and decreases with neoadjuvant therapy. Inhibition of Tie2 with the selective inhibitor, rebastinib, preclinically leads to decreased TMEM doorway function and dissemination in PDAC.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    The application of CDK16 inhibitors in the treatment of triple-negative breast cancer (Section 30; Poster Board #27) -  Mar 14, 2023 - Abstract #AACR2023AACR_6883;    
    Knockdown of CDK16 could significantly suppress tumor growth and metastasis. Furthermore, in our studies, rebastinib acting as a CDK16 inhibitor displayed its strong suppression of TNBC tumor growth in a dose-dependent manner, indicating rebastinib or its analogs could be druggable and likely used to treat TNBC patients.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    TMEM doorways are an actionable target in pancreatic adenocarcinoma (Section 6; Poster Board #20) -  Mar 14, 2023 - Abstract #AACR2023AACR_5453;    
    TMEM doorway concentration is significantly associated with PDAC tumor grade. Inhibition of Tie2 with the selective inhibitor, rebastinib, preclinically leads to decreased TMEM doorway function and dissemination in PDAC.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    Journal:  Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy. (Pubmed Central) -  Sep 4, 2022   
    Finally, we demonstrate that TMEM Activity-MRI increases upon treatment with paclitaxel in mouse models, consistent with prior observations that chemotherapy enhances TMEM doorway assembly and activity in human breast cancer. Our findings suggest that TMEM Activity-MRI is a promising precision medicine tool for localized breast cancer that could be used as a non-invasive test to determine metastatic risk and serve as an intermediate pharmacodynamic biomarker to monitor therapeutic response to agents that block TMEM doorway-mediated dissemination.
  • ||||||||||  Stivarga (regorafenib) / Bayer, rebastinib (DCC-2036) / Deciphera
    Journal, Myeloid-derived suppressor cells, PD(L)-1 Biomarker, IO biomarker:  TIE-2 Signaling Activation by Angiopoietin 2 On Myeloid-Derived Suppressor Cells Promotes Melanoma-Specific T-cell Inhibition. (Pubmed Central) -  Aug 10, 2022   
    Furthermore, by using TIE-2 kinase-specific inhibitors such as regorafenib or rebastinib, we demonstrated that an active TIE-2 signaling was required for optimal suppressive activity of these cells after ANGPT2 exposition. Collectively, these results support that TIE-2 M-MDSC/ANGPT2 axis represents a potential immune escape mechanism in melanoma.
  • ||||||||||  Halaven (eribulin mesylate) / Eisai, rebastinib (DCC-2036) / Ono Pharma
    Trial termination, Metastases:  Rebastinib Plus Antitubulin Therapy With Paclitaxel or Eribulin in Metastatic Breast Cancer (clinicaltrials.gov) -  Apr 4, 2022   
    P1,  N=28, Terminated, 
    CDK16 plays a critical role in TNBC and is a novel promising therapeutic target for TNBC. Recruiting --> Terminated; Unfortunately, Deciphera management decided to not move forward with the rebastinib program and are terminating early.
  • ||||||||||  dorsomorphin (Compound C) / EMD Serono, rebastinib (DCC-2036) / Deciphera
    Tie2-mediated AMPK activation by ferritin-based protein C nanoparticles inhibits advanced prostate cancer development through induction of vasodilation (E-Poster Website) -  Mar 9, 2022 - Abstract #AACR2022AACR_7713;    
    Interestingly, these effects were all abolished by pretreatment with Compound C (an AMPK inhibitor), rebastinib (selective Tie2 Inhibitor), AMPK knockdown using siRNA, or dominant negative AMPKα recombinant adenovirus...In summary, TFMG exerted vasodilatation through activating Tie2/AMPK/eNOS signaling in endothelial cells, which leads to the overcoming vasoconstriction induced ADT. This study provides the potential value of TFMG in vasodilation of blood vessels leading suppression of CRPC development.
  • ||||||||||  Journal:  Impact of Type II LRRK2 inhibitors on signalling and mitophagy. (Pubmed Central) -  Dec 16, 2021   
    Finally, we demonstrate that the LRRK2[A2016T] mutant which is resistant to MLi-2 Type 1 inhibitor, also induces resistance to GZD-824 and Rebastinib suggesting this mutation could be exploited to distinguish off target effects of Type II inhibitors. Our observations provide a framework of knowledge to aide with the development of more selective Type II LRRK2 inhibitors.
  • ||||||||||  olverembatinib (HQP1351) / Ascentage Pharma, rebastinib (DCC-2036) / Deciphera
    Journal:  cAbl Kinase Regulates Inflammasome Activation and Pyroptosis via ASC Phosphorylation. (Pubmed Central) -  Aug 7, 2021   
    Complementation of ASC knockout THP-1 cells with mutated Y146A ASC significantly abrogated inflammasome activation and ASC oligomerization as compared with wild-type ASC complementation. Thus, these findings support cAbl kinase as a positive regulator of inflammasome activity and pyroptosis, likely via phosphorylation of ASC.
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    [VIRTUAL] A phase Ib/II study of rebastinib and paclitaxel in advanced/metastatic platinum-resistant ovarian cancer () -  Jul 22, 2021 - Abstract #ESMO2021ESMO_2061;    
    P1b/2
    All received ≥1 prior regimen with paclitaxel/carboplatin; median number (range) of prior regimens was 4 (2, 7). These updated of rebastinib at 50 mg BID in combination with paclitaxel showed encouraging preliminary antitumor activity and a manageable safety profile in heavily pretreated PROC patients, and supports further development in patients with PROC.
  • ||||||||||  rebastinib (DCC-2036) / Ono Pharma
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  DCC-2036-01-003: A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) -  Apr 22, 2021   
    P1b/2,  N=201, Recruiting, 
    The updated results of rebastinib at 50 mg BID in combination with paclitaxel showed encouraging preliminary anti-tumor activity and an acceptable safety profile in heavily pretreated EC patients, and supports further development in patients with EC (NCT03601897). Trial completion date: Nov 2021 --> Oct 2022 | Trial primary completion date: Nov 2021 --> Oct 2022
  • ||||||||||  rebastinib (DCC-2036) / Deciphera
    Journal:  Imaging of Tie2 with a fluorescently labeled small molecule affinity ligand. (Pubmed Central) -  Jan 15, 2021   
    We found that the Rebastinib-BODIPY TMR (Reb-TMR) derivative has superior imaging characteristics in vitro, and successfully labeled endothelial cells in vivo. We propose that this probe could be further used in in vivo applications for studying the role of Tie2 in disease.
  • ||||||||||  Halaven (eribulin mesylate) / Eisai, rebastinib (DCC-2036) / Ono Pharma
    Enrollment change, Metastases:  Rebastinib Plus Antitubulin Therapy With Paclitaxel or Eribulin in Metastatic Breast Cancer (clinicaltrials.gov) -  Dec 11, 2020   
    P1,  N=24, Recruiting, 
    Five other compounds showed also a negative but small free energy of binding: nikethamide, nifurtimox, rebimastat, apomine and rebastinib. N=60 --> 24
  • ||||||||||  IACS-010759 / UT MD Anderson Cancer Center, Vanflyta (quizartinib) / Daiichi Sankyo
    [VIRTUAL] The Combined Treatment with the FLT3-Inhibitor AC220 and the Complex I Inhibitor Iacs-010759 Synergistically Depletes Wt- and FLT3-Mutated Acute Myeloid Leukemia Cells (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_2919;    
    Thus, we investigated more in-depth the synergism between IACS-010759 (10nM) and 13 FLT3 inhibitors, all currently in clinical trials (AC220, sorafenib, gilteritinib, sunitinib, ponatinib, midostaurin, ibrutinib, TP-0903, crenolanib, tandutinib, FF-10101, lestaurtinib, and KW-2449; 0.0128:5x:5000nM), in AML cell lines (FLT3-wt KG-1, U937, OCI-AML2, OCI-AML3; and FLT3-mutant MOLM-13 and MOLM-14)...Influx inhibition of both the two main carbon sources, glucose and glutamine, was observed leading to impairment of the TCA cycle and glycolysis for energy production, as well as pentose phosphate pathway and de novo nucleotide biosynthesis. In conclusion, we identified a novel drug combination AC220 and IACS-010759 which synergistically inhibits AML cell growth regardless of FLT3 mutation at least by metabolism disruption.
  • ||||||||||  Halaven (eribulin mesylate) / Eisai, rebastinib (DCC-2036) / Ono Pharma
    Trial completion date, Trial primary completion date, Metastases:  Rebastinib Plus Antitubulin Therapy With Paclitaxel or Eribulin in Metastatic Breast Cancer (clinicaltrials.gov) -  Jun 4, 2020   
    P1,  N=60, Recruiting, 
    Clinical trial identification: NCT03717415. Trial completion date: Jul 2020 --> Dec 2021 | Trial primary completion date: Jul 2020 --> Jul 2021
  • ||||||||||  Clinical, Review, Journal:  Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. (Pubmed Central) -  Oct 29, 2019   
    Crystallographic and structure-activity relationship analysis, jointly to clinical data, were pivotal to shed light on this topic. More recently, preclinical evidence on bafetinib, rebastinib, tozasertib, danusertib, HG-7-85-01, GNF-2, and 1,3,4-thiadiazole derivatives lay promising foundations for better inhibitors to be approved for clinic in the near future.Notably, structural mechanisms of action and drug design exemplified by Bcr-Abl inhibitors have broad relevance to both break through resistances in CML treatment and develop inhibitors against other kinases as targeted chemotherapeutics.